We analyzed the biochemical and molecular defects in cultured lymphoblastoid cells that were obtained from 60 Japanese patients with Leigh syndrome. Defects were determined in 30 patients (50%), and 15 patients had enzyme defects ; 5 patients had pyruvate dehydrogenase complex (PDHC), 4 patients had respiratory chain complex I, and 6 patients had cytochrome c oxidase (COX). A point mutation of mitochondrial DNA (mtDNA) was found in 15 patients (A8344G in one, T8993C in two, and T8993G in 12), indicating that cultured lymphoblastoid cells are useful for elucidating the etiology of Leigh syndrome and that mtDNA mutations occured more frequently in Japanese patients with Leigh syndromeIn our study, five of 12 patients with T8993G mutations were associated with West syndrome and only patients with this mutation had West syndrome. These findings suggest that patients with Leigh syndrome associated West syndrome have a high possibility of defects due to T8993G mutations. Four patients with PDHC deficiency showed a reduced affinity for thiamine pyrophosphate, and thiamine treatment resulted in clinical improvements, indicating that these 4 patients have a thiamine-responsive PDHC deficiency and high doses of thiamine may be useful at the early stage of neurologic abnormalities in patients with Leigh syndrome due to this type of PDHC deficiency